Abstract

Guggulsterone [4,17(20)-pregnadiene-3,16-dione], a constituent of Commiphora mukul, is used to treat obesity, diabetes, arthritis, and atherosclerosis. Recently it has been known that guggulesterone isomers (trans or cis) show isomer-specificity in their antileukemic activities in leukemia cells. Here, we investigated whether guggulsterone isomers differently control 12-O-tetradecanoylpho-bol-13-acetate (TPA)-induced MMP-9 expression, and then the combination of these isomers cooperatively inhibits breast cancer invasiveness. Cis-guggulsterone inhibited TPA-induced MMP expression through blocking NF-κB signaling, whereas trans-guggulsterone through blocking MAPK/AP-1 signaling. Cis-guggulsterone was the more potent than trans-guggulsterone in inhibition of TPA-induced MMP-9 expression and cell invasion of MCF-7 cells. Furthermore, we found that the combination of these isomers showed addictive effects on inhibition of cell invasion of MCF-7 cells. These results suggest that guggulesterone controls isomer-specifically TPA-induced MMP-9 expressions and cell invasions of MCF-7 cells. This study is the first to show that combination of guggulsterone isomers might be known as a potential strategy for the medical treatment of breast cancer.